高通量血液透析对非糖尿病尿毒症患者胰岛素抵抗和左室功能的影响

目的观察高通量血液透析对非糖尿病维持性血液透析(MHD)患者胰岛素抵抗及心脏结构和功能的影响。方法选择MHD患者60例,病情稳定,已排除急性感染及其他活动性疾病。随机分为高通量透析组和常规血液透析组,每组30例。治疗6个月,分别观察2组患者治疗前后高敏C反应蛋白(high sensitiving C-reactive protein,hs-CRP)、白介素6(IL-6)和稳态模型胰岛素抵抗指数(HOMA-IR),并应用心脏超声心动图测定患者左心房前后径(LAD),左心室舒张期内径(LVEDd),左心室收缩期内径(LVEDs)左心室舒张期后壁厚度(LVPWT),室间隔厚度(IVST),左心室质量指数(LV-MI),左心室射血分数(LVEF),二尖瓣前向血流E峰与A峰比值(E/A),测量每分心输出量(CO)等。结果 hsCRP、HOMA-IR、IL-6分别与LAD,LVEDd,LVEDs,IVST,LVPWT,LVMI呈正相关(P<0.05),与LVEF、E/A、CO呈负相关(P<0.05)。HOMA-IR与hsCRP、IL-6相互之间呈正相关(P<0.05)。高通量血液透析组hsCRP、IL-6和HOMA-IR与治疗前相比显著下降,差异有统计学意义,而普通血液透析组治疗前后差异无统计学意义。结论 MHD患者存在微炎症状态,高通量血液透析较低通量透析能明显改善非糖尿病维持性血液透析患者胰岛素抵抗,并改善了心脏功能。     

左旋肉碱对维持性血液透析患者胰岛素抵抗的影响

目的　观察左旋肉碱对维持性血液透析患者胰岛素抵抗 (IR)的影响。方法　选择尿毒症维持血液透析患者 4 0例 ,随机分成 2组 ,治疗组 2 0例、对照组 2 0例 ,治疗组于每次透析后静脉注射左旋肉碱1.0g,对照组静脉注射 5ml生理盐水 ,疗程共 12周。另设正常对照组 10例。用空腹血糖与空腹胰岛素浓度乘积的倒数即胰岛素敏感指数 (ISI)作为胰岛素敏感指标。采用放免法测定胰岛素水平。常规方法检测总胆固醇、甘油三脂等指标。结果　治疗组肉碱治疗 12周后患者ISI较治疗前显著提高 (P <0 .0 5 )。对照组ISI无显著性变化。结论　维持性血液透析患者存在IR现象 ,左旋肉碱能改善维持性血液透析患者IR。     

地塞米松对孕妇胰岛素分泌、胰岛素抵抗的影响

目的 :探讨地塞米松 (DEX)促胎儿肺成熟对孕妇胰岛素分泌指数 (IS)、胰岛素敏感指数 (IAI)的影响。方法 :对 1999年 9月至 2 0 0 1年 1月在本院住院的 15 0名需使用地塞米松促胎儿肺成熟孕妇进行研究 ,使用DEX前及用药后 18～ 2 4h抽取肘前静脉血查FPG及FC P。结果 :糖耐量异常者用药后 ,β细胞功能的改变较用药前差异有显著意义 (P <0 0 5 ) ,糖耐量异常者用药后 ,胰岛素敏感性的改变较用药前差异有显著意义 (P <0 0 5 )。结论 :地塞米松促胎儿肺成熟可造成胰岛素分泌指数、胰岛素的敏感性指数的改变 ,从而导致血糖的变化     

小檗碱片对2型糖尿病患者胰岛素分泌及抵抗的影响

目的观察小檗碱片对2型糖尿病患者胰岛素分泌及抵抗的影响。方法纳入病例随机分2组,全部在糖尿病饮食控制下,规律活动。治疗组20例采用常规降糖治疗加口服盐酸小檗碱片0.5g/次,3次/d;对照组20例采用常规降糖治疗,共治疗8w。所有患者于治疗前,后均分别测空腹血糖、空腹胰岛素。以胰岛素分泌指数及稳态模型胰岛素抵抗指数分别评估基础胰岛素分泌功能及胰岛素敏感性。对比分析各组治疗前后的变化。结果改善胰岛素敏感性治疗组疗效优于对照组。结论小檗碱片可以明显改善胰岛素敏感性。     

高通量血液透析对糖尿病肾病维持性血液透析患者胰岛素抵抗的影响

目的 观察高通量血液透析对糖尿病肾病维持性血液透析患者胰岛素抵抗的影响.方法 选择南京医科大学附属无锡人民医院透析中心糖尿病肾病维持性血液透析患者60例,随机分为高通量透析和低通量透析2组,治疗3个月,分别观察2组患者治疗前、后稳态模式评估法评价的胰岛素抵抗指数(homeostasis model assessment of insulin resistance index,HOMA-IR)、白细胞介素6(interleukin6,IL-6)、甲状旁腺素(parathyroid hormone,PTH)、Kt/V等指标的变化.结果 高通量组的HOMA-IR、IL-6、PTH均较治疗前有显著下降(P＜0.05),而低通量组的HOMA-IR、IL-6、PTH治疗前后差异无统计学意义(P＞0.05).结论 高通量透析较低通量透析能明显改善糖尿病肾病终末期肾衰竭维持性血液透析患者的胰岛素抵抗.     

新诊断的2型糖尿病患者血糖水平与胰岛素分泌及胰岛素抵抗的关系

目的:比较不同糖化血红蛋白(HbA1c)水平的新诊断的2型糖尿病(T2DM)患者胰岛素分泌功能和胰岛素抵抗(IR)情况。方法:将235例新诊断为T2DM的患者按HbA1c水平分为3组,即HbA1c组1(HbA1c≤7.5%)、HbA1c组2(7.5%相似文献   

尿毒症患者血液透析前后血胰岛素样生长因子-1水平的变化及意义

目的探讨尿毒症患者血液透析 ( HD)前后血胰岛素样生长因子 -1( IGF-1)水平变化规律及意义。方法对 3 0例尿毒症患者 HD前、后的血清 IGF-1、尿素氮 ( BUN)、肌酐 ( Cr)、钙 ( Ca)、磷 ( P)等指标进行比较 ,并与正常对照组 ( 15例 )进行比较。结果尿毒症患者HD前后血清 IGF-1水平 [( 1.2 9± 0 .83 ) ng/ml、( 1.5 6± 0 .63 ) ng/ml]显著低于正常对照组 ( 2 .67± 1.71) ng/ml( P<0 .0 1) ,而 HD后水平显著高于 HD前水平 ( P<0 .0 5 )。 HD前 IGF -1水平与 BUN、Scr、Ca、P无显著相关性 ( P>0 .0 5 )。结论 HD可一过性提高尿毒症患者血清 IGF-1水平 ,在某种程度上有助于改善患者的营养不良 ,但作用不持久 ,其临床意义有待进一步探讨。     

严重脓毒症患者胰岛素抵抗和胰岛素分泌功能的观察

目的探讨严重脓毒症患者入ICU后血糖、胰岛素浓度、胰岛素抵抗（IR）及胰岛素分泌功能的动态变化．与疾病的严重程度和预后的关系。方法选取严重脓毒症患者36例和正常对照20例,根据脓毒症后28d后的存活情况,分为生存组（n=20例）和死亡组（n=16）。回顾分析各组第1天、第28天空腹血糖（FBG）、胰岛素（FINS）浓度,使用稳态模式法（HOMA）计算胰岛素抵抗指数（HOMA—IR）及胰岛素分泌指数（HOMA-8）。结果严重脓毒症患者入组后第1天FBG、FINS浓度及HOMA—IR均明显高于对照组,HOMA—β明显低于对照组,差异均有统计学意义（t分别=7．46、5．64、7．07、6．73,P均〈0．05）。生存组与死亡组入组后第1天FBG、FINS浓度及HOMA—IR均高于对照组,而HOMA—β低于对照组,差异有统计学意义（t分别=5．13、4．43、5．49、4．70、6．85、3．60、5．02、8．96,P均〈0．05）;生存组第28天FBG、FINS浓度及HOMA—IR较第1天下降,而HOMA-β回升,差异均有统计学意义（t分别=3．71、2．72、4．06、2．47,P均〈0．05）;死亡组FBG和HOMA-IR高于生存组,HOMA—β低于生存组,差异有统计学意义（t分别=3．46、2．82、2．97,P均〈0．05）;而FINS浓度与生存组间差异无统计学意义（t=0．32,P〉0．05）。单个脏器功能不全患者FBG浓度、HOMA-β与对照组间比较,差异均无统计学意义（q分别=1．95、1．66,P均〉0．05）;多个脏器功能不全患者FBG、FINS浓度及HOMA—IR均高于对照组;而HOMA—β低于对照组,差异均有统计学意义（q分别=10．18、5．19、7．58、14．96,P均〈0．05）。APACHEⅡ评分与FBG、HOMA—IR呈正相关,与HOMA—β呈负相关,差异均有统计学意义（r分别=0．68、0．50、-0．66,P均〈0．05）。结论严重脓毒症患者存在IR,其中多脏器功能不全患者存在胰岛β细胞功能不全,FBG浓度、HOMA—IR及HOMA—β可作为判断严重脓毒症患者病情转归,预后的预警指标。     

2型糖尿病患者糖化血红蛋白水平与胰岛素分泌及胰岛素抵抗的关系

目的 比较不同糖化血红蛋白(HbA1c)水平的2型糖尿病(T2DM)患者胰岛素分泌和胰岛素抵抗情况,了解葡萄糖毒性对胰岛β细胞分泌功能的影响。方法 将137例T2DM患者,按HbA1c水平分为4组,即A组(HbA1c≤7%),B组(7%11%),测定各组空腹血糖(FPG),HbA1c及精氨酸刺激前后各时点的胰岛素(INS)。用稳态模型评估法评价基础胰岛素分泌功能(HOMA-β)和胰岛素抵抗指数(HOMA-IR),并用精氨酸刺激后血糖校正胰岛素增值(△INS/FPG)评估第一相胰岛素分泌功能。结果 各组T2DM患者FPG差异均有统计学意义(F=15.633～106.154,P值均<0.01),且与HbA1c呈正相关(r=0.627,P<0.01); HOMA-β和△INS/FPG均表现为A组、B组分别与其他各组差异有统计学意义(F=4.106～16.255,P值均<0.05),但C组与D组之间差异无统计学意义(F=0.761,2.756,P值均>0.05); A组HOMA-IR与C组、D组之间差异有统计学意义(F=4.836,8.524,P值均<0.05); 精氨酸刺激后胰岛素分泌不足检出率在HbA1c>9%时明显升高。结论 胰岛β细胞功能的判断受长期糖毒性的干扰,故将T2DM患者的HbA1c控制在9%以下进行胰岛素分泌功能评估及精氨酸刺激试验,能较为准确地反映胰岛β细胞功能。     

Effect of 1,25-dihydroxyvitamin D3 on mesangial cell proliferation

We have studied the effect of 1,25-dihydroxyvitamin D3 (1,25, (OH)2D3) on mesangial cell growth. Previous studies have shown that the monocyte-macrophage is the principal effector cell in immune-mediated nephritis; this cell infiltrates the glomerular mesangium, and its products may have important effects on the physiology of the mesangial cell. One of the substances produced by the activated macrophage is 1,25,(OH)2D3. We have investigated the effect of 1,25,(OH)2D3 on mesangial cell growth and found that this vitamin D metabolite suppresses the proliferation of mouse mesangial cells as assessed by mesangial cell tritiated thymidine uptake and by cell counts; this substance also antagonizes the mitogenic effect of epidermal growth factor on mesangial cell growth. By comparison, the vitamin D metabolite 25 hydroxyvitamin D3 has no significant suppressive effect on the proliferation of mesangial cells. It has also been possible to demonstrate that 1,25,(OH)2D3 could suppress the growth of mesangial cells that had been committed to proliferate by the prior addition of epidermal growth factor. The results of these studies are relevant to our understanding of the pathogenesis of the cellular abnormalities that occur in immune-mediated nephritis, and especially in subjects who have concurrent hypertension, because a segment of subjects with hypertension have demonstrable abnormalities in the levels of circulating 1,25,(OH)2D3.     

Defective binding and function of 1,25-dihydroxyvitamin D3 receptors in peripheral mononuclear cells of patients with end-organ resistance to 1,25-dihydroxyvitamin D.

Lectin-induced DNA synthesis by peripheral mononuclear cells from 17 normal donors was inhibited (40-60%) by 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) at physiological concentrations (10(-10)-10(-9) M). The lymphocytes acquire specific receptors for 1,25(OH)2D3 upon activation by the lectins. This process precedes the inhibitory effect of 1,25(OH)2D3. We studied lymphocytes from six patients from four different kindreds with the syndrome of hereditary end-organ resistance to 1,25(OH)2D (the so-called vitamin D-dependent rickets type II). In five patients (three kindreds) peripheral blood mononuclear cells did not acquire receptors for 1,25(OH)2D3 upon phytohemagglutinin-induced activation. Moreover, in contrast to normal lymphocytes, the mitogenic stimulation of these patients' lymphocytes by phytohemagglutinin and concanavalin A was not inhibited by 1,25(OH)2D3. Activated lymphocytes of the sixth patient from a fourth kindred exhibited normal binding of [3H]1,25(OH)2D3 but the hormone failed to inhibit the mitogenic stimulation. A similar pattern of the vitamin D effector system was previously observed in fibroblasts cultured from skin biopsies of the same group of patients. The conclusions from these findings are: (a) the inhibition of mitogenic stimulation by 1,25(OH)2D3 is mediated by specific functional receptors to the hormone; and (b) the receptors for 1,25(OH)2D3 in mononuclear cells are probably controlled genetically by the same mechanisms as the effector system in well-characterized target organs of the hormone, such as intestine and kidney.     

Enterohepatic physiology of 1,25-dihydroxyvitamin D3.

After intravenous administration of radiolabeled 1,25-dihydroxyvitamin D3 to rats, approximately 25% of the administered radioactivity appeared in the bile within 24 h. Instillation of the biliary radioactivity into the duodena of other rats was followed by recovery of 15% of the radioactivity in newly secreted bile within 24 h. The process by which products of 1,25-dihydroxyvitamin D3 were excreted in bile was not saturable in the dose range tested (0.275-650 ng). The metabolites of 1,25-dihydroxyvitamin D3 present in bile were found to be much more polar than 1,25-dihydroxyvitamin D3 and were resolved into three fractions on high performance liquid chromatography. 60% of the radioactivity present in bile was retained selectively by DEAE-cellulose; the radioactive material could be eluted from the gel at a low pH or at high salt concentrations. When bile containing the radiolabeled metabolites was incubated at 37 degrees C and pH 5 with beta-glucuronidase, there was an increase in the amount of radioactivity comigrating with 1,25-dihydroxyvitamin D3. Treatment of the products of radiolabeled 1,25-dihydroxyvitamin D3 in bile with diazomethane, an agent which converts acids into methyl esters, transformed one of the metabolites into a less polar compound. These results demonstrate that there is a quantitatively important enterophepatic circulation of the products of 1,25-dihydroxyvitamin D3 in the rat.     

1,25-二羟维生素D3治疗对早期糖尿病肾病炎性因子的影响

目的 探讨早期糖尿病肾病( diabetic nephropathy,DN)患者体内1,25-二羟维生素D3与血清炎性因子水平的变化,观察1,25-二羟维生素D3对早期DN患者相关炎性因子的影响.方法 2型糖尿病患者238例中无蛋白尿者100例为DM组,初诊早期DN者138例为DN组,DN组再随机分为治疗组和对照组各69例.在血糖、血压稳定1周后治疗组给予常规治疗+骨化三醇胶丸,对照组给予常规治疗,2组疗程均为3个月.比较各组患者1,25-二羟维生素D3、24 h尿蛋白定量及相关炎性因子的变化.结果 治疗前DN组1,25-二羟维生素D3水平低于DM组(P＜0.05),白细胞介素-6、肿瘤坏死因子-α、血浆纤溶酶原激活物抑制物-1及尿结缔组织生长因子水平均高于DM组(P＜0.05);治疗后DN治疗组上述炎性因子水平及24 h尿蛋白定量均较治疗前降低(P＜0.05),1,25-二羟维生素D3水平升高(P＜0.05),对照组治疗前、后各指标比较差异均无统计学意义(P＞0.05).结论 早期DN患者1,25-二羟维生素D3缺乏,炎性因子水平高,补充骨化三醇胶丸可改善患者炎症状态.     

Effects of ultrasound and 1,25-dihydroxyvitamin D3 on growth factor secretion in co-cultures of osteoblasts and endothelial cells

It has been shown that low-intensity pulsed ultrasound (US) accelerates fracture healing in animal models and in clinical studies. However, the mechanism by which US accelerates fracture healing remains unclear. Systemic factors and several growth factors, such as platelet-derived growth factor (PDGF), are thought to be involved in the process of fracture healing. In the present study, we examined the effects of US and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on growth factor secretion in a co-culture system of human osteoblastic cells (SaOS-2) and endothelial cells (HUVEC). US was applied to cultured cells for 20 min daily for four consecutive days. US treatment increased the PDGF-AB level in the conditioned media. 1,25-(OH)2D3 (1 x 10(-8) M) also enhanced PDGF-AB secretion. The secretion of PDGF-AB was synergistically increased by the combination of US and 1,25-(OH)2D3. These results suggest that the stimulation of growth factor secretion from cells by US and 1,25-(OH)2D3 treatment may be involved in the acceleration of fracture healing.     

1,25（OH）2D3对大鼠肾小球系膜细胞凋亡的影响

目的探讨1,25一二羟基维生素D3[1,25(OH)2D3]对大鼠系膜细胞增殖与凋亡及其相关基因Fas表达的影响。方法体外培养的大鼠系膜细胞,分为正常对照组(0 mol/L)和不同浓度1,25(OH)2D3干预组(10-10mol/L;10-8mol/L;10-6mol/L),采用四甲基偶氮唑蓝(MTT)比色法及流式细胞仪,检测不同作用时间(24 h、48 h)下,系膜细胞增殖及凋亡情况,免疫荧光染色法观察干预24 h后,凋亡相关基因Fas的表达情况并测定各组荧光强度。结果与正常对照组相比,1,25(OH)2D3干预组,可明显抑制系膜细胞增殖,促进凋亡,并呈作用时间依赖性。同时免疫荧光染色证实干预浓度越大,系膜细胞内Fas表达增多,荧光强度增高,差异有统计学意义(P<0.01)。结论 1,25(OH)2D3干预大鼠肾小球系膜细胞,能抑制细胞增殖,促进细胞凋亡,Fas的表达增多,呈浓度和时间依赖性。     

Effect of 1,25-dihydroxyvitamin D deficiency on the metabolic clearance rate of 1,25-dihydroxyvitamin D3: studies using pigs with vitamin D-dependent rickets type 1

We have used pigs with inherited vitamin D-dependent rickets type 1 to study the effect of 1,25-dihydroxyvitamin D deficiency on the metabolic clearance rate of 3H-1,25-dihydroxyvitamin D3 infused to steady-state levels in plasma. Plasma levels of 1,25-dihydroxyvitamin D were 24 +/- 1 (SEM) pmol/l in the hypocalcaemic, homozygous piglets and 196 +/- 27 pmol/l in their normocalcaemic, heterozygous siblings. The metabolic clearance rate of 1,25-dihydroxyvitamin D3 was the same in both normal heterozygous (0.90 +/- 0.02) and hypocalcaemic, homozygous piglets (0.90 +/- 0.01 ml-1 min-1 kg-1 metabolic body size). We conclude that a deficiency of circulating 1,25-dihydroxyvitamin D does not influence the clearance of 1,25-dihydroxyvitamin D3 from the circulation of pigs.     

Differential effects of 19-nor-1,25-dihydroxyvitamin D(2) and 1,25-dihydroxyvitamin D(3) on intestinal calcium and phosphate transport

19-Nor-1,25-dihydroxyvitamin D(2) (19-norD(2)) a less calcemic and phosphatemic analog of 1,25-dihydroxyvitamin D (1,25[OH](2)D(3)), is approved for the treatment of secondary hyperparathyroidism in patients with kidney failure. We have previously demonstrated that 19-norD(2) is less active than 1,25(OH)(2)D(3) in stimulating bone resorption. In this study, we compared the potencies of 19-norD(2) and 1,25(OH)(2)D(3) in stimulating net calcium and phosphate absorption in the intestine. Mineral balance was assessed in normal rats during the last 4 days of a 14-day treatment with various daily doses of 19-norD(2) or 1,25(OH)(2)D(3). Calcium absorption increased from 16.5% +/- 7.8% in vehicle-treated rats to 27.5% +/- 7.2% in rats given 10 ng/day 1,25(OH)(2)D(3) and to 21.6% +/- 3.9%, 26.2% +/- 5.5%, and 27.4% +/- 5.1% in rats treated with 10, 50, and 100 ng/day 19-norD(2), respectively. Thus comparable stimulation of calcium transport was attained with 10 ng 1,25(OH)(2)D(3) and 100 ng 19-norD(2). Similar results were obtained for phosphate absorption, with an increase from 28.2% +/- 5.5% in vehicle-treated rats to 40.2% +/- 4.7% in rats given 10 ng/day 1,25(OH)(2)D(3) and to 32.9% +/- 2.2%, 36.2% +/- 4.5%, and 36.8% +/- 3.8% in rats given 10, 50, and 100 ng/day 19-norD(2), respectively. Vitamin D compounds are believed to increase calcium absorption by inducing a calcium channel (epithelial calcium transporter or calcium transporter-1 [CaT1]) on the luminal membrane, a calcium-binding protein (Calbindin D9k) in the cytosol, and a calcium pump (plasma membrane calcium adenosine triphosphatase-1 [PMCA1]) on the basolateral membrane. Northern-blot analysis of intestinal ribonucleic acid of vitamin D-deficient rats given seven daily injections of vehicle or 100 ng 1,25(OH)(2)D(3) or 19-norD(2) revealed that 19-norD(2) was less potent than 1,25(OH)(2)D(3) in stimulating expression of CaT1, Calbindin D9k and PMCA1. In summary, the reduced calcemic and phosphatemic activities of 19-norD(2) can be attributed to lower potency in stimulating intestinal calcium and phosphate absorption.